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Protein

F-box/WD repeat-containing protein 7

Gene

Fbxw7

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination. Identified substrates include cyclin-E (CCNE1 or CCNE2), JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1 and probably PSEN1. Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation. SCF(FBXW7) complex mediates the ubiquitination and subsequent degradation of NFE2L1. Involved in bone homeostasis and negative regulation of osteoclast differentiation.By similarity

GO - Biological processi

  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-RNO-8951664 Neddylation
R-RNO-983168 Antigen processing: Ubiquitination & Proteasome degradation

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/WD repeat-containing protein 7Curated
Gene namesi
Name:Fbxw7Imported
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi2321145 Fbxw7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004420301 – 713F-box/WD repeat-containing protein 7Add BLAST713

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei211PhosphothreonineBy similarity1
Modified residuei233PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Thr-211 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation.By similarity
Ubiquitinated: autoubiquitinates following phosphorylation at Thr-211 and subsequent interaction with PIN1. Ubiquitination leads to its degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiD3Z902
PeptideAtlasiD3Z902

Expressioni

Gene expression databases

BgeeiENSRNOG00000010889
ExpressionAtlasiD3Z902 baseline and differential

Interactioni

Subunit structurei

Homodimer; homodimerization plays a role in substrate binding and/or ubiquitination and degradation (By similarity). Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7 (By similarity). Interacts (via F-box domain) with SKP1. Interacts (via F-box domain) with pseudophosphatase STYX; the interaction is direct and prevents FBXW7 interaction with SKP1 (By similarity). Interacts with cyclin-E (CCNE1 or CCNE2) (By similarity). Interacts with PSEN1 (By similarity). Forms a trimeric complex with NOTCH1 and SGK1 (By similarity). Interacts with NOTCH1 intracellular domain/NICD and NOTCH4 intracellular domain/NICD (By similarity). Interacts with NOTCH2 intracellular domain (N2ICD) (By similarity). Interacts with MYC (when phosphorylated) (By similarity). Interacts with USP28, leading to counteract ubiquitination of MYC (By similarity). Interacts (when phosphorylated at Thr-211) with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (By similarity). Interacts with UBE2QL1 (By similarity). Interacts with FAM83D; promotes FBXW7 degradation (By similarity). Interacts with MYCN; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (By similarity). Interacts with JUN (By similarity). Found in a complex with JUN and PRR7 (PubMed:27458189). Interacts with JUN and PRR7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (By similarity). Interacts with NFE2L1 (By similarity).By similarity1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000050193

Structurei

3D structure databases

ProteinModelPortaliD3Z902
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini284 – 330F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati384 – 424WD 1Sequence analysisAdd BLAST41
Repeati426 – 462WD 2Sequence analysisAdd BLAST37
Repeati465 – 504WD 3Sequence analysisAdd BLAST40
Repeati506 – 542WD 4Sequence analysisAdd BLAST37
Repeati545 – 584WD 5Sequence analysisAdd BLAST40
Repeati586 – 624WD 6Sequence analysisAdd BLAST39
Repeati628 – 665WD 7Sequence analysisAdd BLAST38

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili94 – 136Sequence analysisAdd BLAST43

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi96 – 127Glu-richPROSITE-ProRule annotationAdd BLAST32

Domaini

The WD repeats mediate interaction with substrates of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.By similarity
The F-box domain mediates interaction with SKP1.By similarity

Keywords - Domaini

Coiled coil, Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0274 Eukaryota
ENOG410XRWX LUCA
GeneTreeiENSGT00760000119106
InParanoidiD3Z902
OrthoDBiEOG091G04EW

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR020472 G-protein_beta_WD-40_rep
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF12937 F-box-like, 1 hit
PF00400 WD40, 7 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SM00320 WD40, 8 hits
SUPFAMiSSF50978 SSF50978, 1 hit
SSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit
PS00678 WD_REPEATS_1, 5 hits
PS50082 WD_REPEATS_2, 7 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequencei

Sequence statusi: Complete.

D3Z902-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNQELLSVGS KRRRTGGSLR GNASSSQVDE EQMNRVVEED PQQQPRHQEE
60 70 80 90 100
EHTARNGELV GADPRPGAQN DSQQGQVEEN NNRFVSVDED SSGNQEEQEE
110 120 130 140 150
DEEHAGEQEE EEEEEEEEEE EEEMDQESDD FDQSDDSSRE DEHTHNSNVT
160 170 180 190 200
NCTSVVDLPI NQLSSPFYTK TTKMKRKLDH GSEVRSFSLG KKPCKVSDYT
210 220 230 240 250
STTGLVPCSA TPTTFGDLRA ANGQGQQRRR ITSVQPPTGL QEWLKMFQSW
260 270 280 290 300
SGPEKLLALD ELIDSCEPTQ VKHMMQVIEP QFQRDFISLL PKELALYVLS
310 320 330 340 350
FLEPKDLLQA AQTCRYWRIL AEDNLLWREK CKEEGIDEPL HIKRRKIIKP
360 370 380 390 400
GFIHSPWKSA YIRQHRIDTN WRRGELRSPK VLKGHDDHVI TCLQFCGNRI
410 420 430 440 450
VSGSDDNTLK VWSAVTGKCL RTLVGHTGGV WSSQMRDNII ISGSTDRTLK
460 470 480 490 500
VWNAETGECI HTLYGHTSTV RCMHLHEKRV VSGSRDATLR VWDIETGQCL
510 520 530 540 550
HVLMGHVAAV RCVQYDGRRV VSGAYDFMVK VWDPETETCL HTLQGHTNRV
560 570 580 590 600
YSLQFDGIHV VSGSLDTSIR VWDVETGNCI HTLTGHQSLT SGMELKDNIL
610 620 630 640 650
VSGNADSTVK IWDIKTGQCL QTLQGPSKHQ SAVTCLQFNK NFVITSSDDG
660 670 680 690 700
TVKLWDLKTG EFIRNLVTLE SGGSGGVVWR IRASNTKLVC AVGSRNGTEE
710
TKLLVLDFDV DMK
Length:713
Mass (Da):80,367
Last modified:April 3, 2013 - v2
Checksum:i3B208792FE3790B9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR07012054 Genomic DNA No translation available.
AABR07012055 Genomic DNA No translation available.
AABR07012056 Genomic DNA No translation available.
UniGeneiRn.13083

Genome annotation databases

EnsembliENSRNOT00000052051; ENSRNOP00000050193; ENSRNOG00000010889

Similar proteinsi

Entry informationi

Entry nameiFBXW7_RAT
AccessioniPrimary (citable) accession number: D3Z902
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2017
Last sequence update: April 3, 2013
Last modified: June 20, 2018
This is version 66 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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